Selection Pressure Required for Long-Term Persistence of bla _CMY-2 -Positive IncA/C Plasmids

Abstract

Multidrug resistance bla CMY-2 plasmids that confer resistance to expanded-spectrum cephalosporins have been found in multiple bacterial species collected from different hosts worldwide. The widespread distribution of bla CMY-2 plasmids may be driven by antibiotic use that selects for the dissemination and persistence of these plasmids. Alternatively, these plasmids may persist and spread in bacterial populations in the absence of selection pressure if a balance exists among conjugative transfer, segregation loss during cell division, and fitness cost to the host. We conducted a series of experiments (both in vivo and in vitro) to study these mechanisms for three bla CMY-2 plasmids, peH4H, pAR060302, and pAM04528. Results of filter mating experiments showed that the conjugation efficiency of bla CMY-2 plasmids is variable, from <10؊7 for pAM04528 and peH4H to ϳ10 ؊3 for pAR060302. Neither peH4H nor pAM04528 was transferred from Escherichia coli strain DH10B, but peH4H was apparently mobilized by the coresident trimethoprim resistance-encoding plasmid pTmpR. Competition studies showed that carriage of bla CMY-2 plasmids imposed a measurable fitness cost on the host bacteria both in vitro (0.095 to 0.25) and in vivo (dairy calf model). Long-term passage experiments in the absence of antibiotics demonstrated that plasmids with limited antibiotic resistance phenotypes arose, but eventually drug-sensitive, plasmid-free clones dominated the populations. Given that plasmid decay or loss is inevitable, we infer that some level of selection is required for the long-term persistence of bla CMY-2 plasmids in bacterial populations.

Modeling the Infection Dynamics of Bacteriophages in Enteric Escherichia coli: Estimating the Contribution of Transduction to Antimicrobial Gene Spread

“…There was no plasmid loss by the bacteria (23,32). The plasmid-bearing bacteria experienced a fitness cost represented by a fractional reduction of 0.05 (23,33) in the maximum growth rate, r. Plasmid transfer was a frequency-dependent transmission process; the number of plasmid-free E. coli bacteria acquiring the gene through plasmid conjugation was ␤(N plϩ ϫ N plϪ /N tot ) (23). The value of ␤ was 0.004/hour and corresponded to the dynamics of transfer of the exemplar bla CMY-2 (23).…”

Conjugation is necessary for a bacterial plasmid to survive under protozoan predation

“…When the benefits of carriage outweigh the costs, plasmids can be maintained by positive selection [4], although over longer time-scales, beneficial accessory genes may be selected to relocate to the chromosome [5]. When the costs outweigh the benefits, plasmids should be lost to purifying selection [6], unless this is counteracted by sufficiently high rates of conjugative transfer or sufficiently rapid compensatory evolution to ameliorate the cost of carriage [7,8].…”

Influence of Therapeutic Ceftiofur Treatments of Feedlot Cattle on Fecal and Hide Prevalences of Commensal Escherichia coli Resistant to Expanded-Spectrum Cephalosporins, and Molecular Characterization of Resistant Isolates

“…In vitro experiments have demonstrated that carriage of bla CMY-2 IncA/C plasmids imposes a fitness cost on the host bacteria, leading to the conclusion that long-term maintenance of IncA/C plasmids requires selective pressure (25). A mathematical model of ESC r E. coli populations in cattle suggests that E. coli strains harboring bla CMY-2 IncA/C plasmids could persist during periods of low selective pressure even if they grow slower than other com-mensal E. coli strains if frequent horizontal transfer of bla CMY-2 IncA/C plasmids occurs or a sufficient fraction of E. coli bacteria ingested by cattle contain bla CMY-2 IncA/C plasmids (26).…”